Efficacy of Nitric Oxide Administration in Attenuating Ischemia/Reperfusion Injury During Neonatal Cardiopulmonary Bypass

2020 ◽  
Vol 11 (4) ◽  
pp. 417-423 ◽  
Author(s):  
Chawki Elzein ◽  
Cynthia Urbas ◽  
Bonnie Hughes ◽  
Yi Li ◽  
Cheryl Lefaiver ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Cardiopulmonary Bypass ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Controlled Trial ◽  
Postoperative Recovery ◽  
Norwood Procedure ◽  
Protective Effects ◽  
Aortic Cross Clamp Time ◽  
To Receive

Objective: Nitric oxide (NO) plays several protective roles in ischemia/reperfusion (I/R) injury. Neonates undergoing the Norwood procedure are subject to develop I/R injury due to the immaturity of their organs and the potential need to interrupt or decrease systemic flow during surgery. We hypothesized that NO administration during cardiopulmonary bypass (CPB) ameliorates the I/R and could help the postoperative recovery after the Norwood procedure. Methods: Twenty-four neonates who underwent a Norwood procedure were enrolled in a prospective randomized blinded controlled trial to receive NO (12 patients) or placebo (12 patients) into the oxygenator of the CPB circuit during the Norwood procedure. Markers of I/R injury were collected at baseline (T0), after weaning from CPB before modified ultrafiltration (T1), after modified ultrafiltration (T2), and at 12 hours (T3) and 24 hours (T4) after surgery, and they were compared between both groups, as well as other postoperative clinical variables. Results: There was no difference in age, weight, anatomical diagnosis, CPB, and aortic cross-clamp time between both groups. Troponin levels were lower in the study group at T1 (0.62 ± 58 ng/mL vs 0.87 ± 0.58 ng/mL, P = .31) and became significantly lower at T2 (0.36 ± 0.32 ng/mL vs 0.97 ± 0.48 ng/mL, P = .009).There were no significant differences between both groups for all other markers. Despite a lower troponin level, there was no difference in inotropic scores or ventricular function between both groups. Time to start diuresis, time to sternal closure and extubation, and intensive care unit and hospital stay were not different between both groups. Conclusion: Systemic administration of NO during the Norwood procedure has myocardial protective effects (lower Troponin levels) but we observed no effect on postoperative recovery. Larger sample size may be needed to show clinical differences.

Protective Effect of Nitric Oxide Pathway in L-Citrulline Renal Ischemia-Reperfusion Injury in Rats

2013 ◽  
Vol 634-638 ◽  
pp. 1357-1361
Author(s):  
Xin Ling ◽  
Xiao Bin Fu ◽  
Li Liu ◽  
Xia Tian ◽  
Ling Yan Sun ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Renal Cortex ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Renal Ischemia ◽  
Protective Effects ◽  
Significant Protection ◽  
Renal Ischemia Reperfusion Injury ◽  
Reperfusion Period ◽  
Oxide Synthase

To observe the protective effects of L-citrulline on the renal ischemia-reperfusion (I/R) injury and elucidate the mechanisms involved. Forty-eight rats were randomized into eight groups. At the end of the reperfusion period, serum was collected and the kidneys were removed for histological and biochemical examinations. Our results showed that pretreatment with L-citrulline significantly ameliorated the renal injury caused by I/R. Moreover, L-citrulline increased the levels of NO. The I/R-induced decreases in total nitric oxide synthase (NOS) activity, inducible NOS activity and constitutive NOS activity in the renal cortex were significantly prevented. These results suggested that L-citrulline administration exhibited significant protection on renal I/R injury.

scholarly journals Influence of Hypoxic and Hyperoxic Preconditioning on Endothelial Function in a Model of Myocardial Ischemia-Reperfusion Injury with Cardiopulmonary Bypass (Experimental Study)

2020 ◽  
Vol 21 (15) ◽  
pp. 5336
Author(s):  
Irina A. Mandel ◽  
Yuri K. Podoksenov ◽  
Irina V. Suhodolo ◽  
Darya A. An ◽  
Sergey L. Mikheev ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Cardiopulmonary Bypass ◽  
Endothelial Function ◽  
Light Microscopy ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Control Group ◽  
Endothelin 1 ◽  
Nitric Oxide Metabolites

The aim of the experiment was to evaluate the effect of preconditioning based on changes in inspiratory oxygen fraction on endothelial function in the model of ischemia-reperfusion injury of the myocardium in the condition of cardiopulmonary bypass. The prospective randomized study included 32 rabbits divided into four groups: hypoxic preconditioning, hyperoxic preconditioning, hypoxic-hyperoxic preconditioning, and control group. All animals were anesthetized and mechanically ventilated. We provided preconditioning, then started cardiopulmonary bypass, followed by induced acute myocardial infarction (ischemia 45 min, reperfusion 120 min). We investigated endothelin-1, nitric oxide metabolites, asymmetric dimethylarginine during cardiopulmonary bypass: before ischemia, after ischemia, and after reperfusion. We performed light microscopy of myocardium, kidney, lungs, and gut mucosa. The endothelin-1 level was much higher in the control group than in all preconditioning groups after ischemia. The endothelin-1 even further increased after reperfusion. The total concentration of nitric oxide metabolites was significantly higher after all types of preconditioning compared with the control group. The light microscopy of the myocardium and other organs revealed a diminished damage extent in the hypoxic-hyperoxic preconditioning group as compared to the control group. Hypoxic-hyperoxic preconditioning helps to maintain the balance of nitric oxide metabolites, reduces endothelin-1 hyperproduction, and enforces organ protection.

Invited Commentary: Efficacy of Nitric Oxide Administration During Neonatal Cardiopulmonary Bypass

2020 ◽  
Vol 11 (4) ◽  
pp. 424-425
Author(s):  
Christoph P. Hornik
Keyword(s):  
Nitric Oxide ◽  
Cardiopulmonary Bypass ◽  
Bypass Surgery ◽  
Controlled Trial ◽  
Norwood Procedure ◽  
Original Research ◽  
Original Research Article ◽  
Research Article ◽  
Cardiopulmonary Bypass Surgery

This editorial accompanies an original research article by Dr Elzein and colleagues describing findings of a randomized, placebo-controlled trial of nitric oxide administration during cardiopulmonary bypass surgery in infants undergoing the Norwood procedure.

scholarly journals The Protective Effects ofαB-Crystallin on Ischemia-Reperfusion Injury in the Rat Retina

2017 ◽  
Vol 2017 ◽  
pp. 1-10 ◽  
Author(s):  
Huan Yan ◽  
Yanli Peng ◽  
Wei Huang ◽  
Liyan Gong ◽  
Li Li
Keyword(s):  
Nitric Oxide ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ganglion Cells ◽  
Ischemia Reperfusion ◽  
Protective Effects ◽  
Retinal Ganglion ◽  
Hematoxylin And Eosin ◽  
Nf Kappab ◽  
Oxide Synthase

To investigate whetherαB-crystallin protects against acute retinal ischemic reperfusion injury (I/R) and elucidate the potential antioxidant mechanisms. Retinal I/R injury was made by elevating the intraocular pressure (IOP) 110 mmHg for 60 min, andαB-crystallin (1 × 10−5 g/L) or vehicle solution was administered intravitreously immediately after I/R injury. The animal was sacrificed 24 h, 1 w, and 1 m after the I/R injury. The retina damage was detected by hematoxylin and eosin (HE) staining and electroretinography (ERG). The level of malondialdehyde (MDA), nitric oxide (NO), and the total superoxide dismutase (T-SOD) was determined. An immunohistochemical study was performed to detect the activation of inducible nitric oxide synthase (iNOS) and NF- (nuclear factor-) kappaB (NF-κB) p65. The decrease of retinal thickness and the number of retinal ganglion cells (RGCs) can be suppressed byαB-crystallin. And the amplitudes of a- and b-wave were remarkably greater withoutαB-crystallin. Similarly,αB-crystallin also significantly decreased the level of MDA and NO and enhanced the activities of T-SOD. The positive expression of iNOS and NF-kappaB p65 was obviously reduced while treated withαB-crystallin.αB-crystallin can inhibit the expression of NF-κB and its antioxidative effect to protect the retina from I/R injury.

scholarly journals Protective Effects of Total Flavones of Rhododendra on Cerebral Ischemia Reperfusion Injury

2008 ◽  
Vol 36 (02) ◽  
pp. 343-354 ◽  
Author(s):  
Yan Guo ◽  
Zhi-Wu Chen
Keyword(s):  
Nitric Oxide ◽  
Cerebral Ischemia ◽  
Nitric Oxide Synthase ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Protective Effects ◽  
Cerebral Ischemia Reperfusion ◽  
Cerebral Ischemia Reperfusion Injury ◽  
Oxide Synthase

This study was to investigate the protective effects and possible mechanisms of total flavones of rhododendra (TFR) against cerebral ischemia reperfusion injury in rats and mice. Cerebral ischemia/reperfusion injury was induced by occluding the right middle cerebral artery (MCA). Infarct volume, neurological deficit, brain water content, levels of malondialdehyde (MDA), nitric oxide (NO) contents, lactate dehydrogenase (LDH) activity in plasma and brain, levels of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities and mRNA expression of inducible nitric oxide synthase (iNOS), neuronal nitric oxide synthase (nNOS) and endothelial nitric oxide synthase (eNOS) in brain were evaluated 7 or 10 days after treatment. TFR significantly reduced infarct volume, ameliorated the neurological deficit and reduced the brain water content. The activities of SOD, LDH and GPX in brain were enhanced, while the activity of LDH in plasma and the contents of MDA and NO in plasma and brain were decreased. While, the expression of iNOS and nNOS mRNA in brain were down-regulated, the expression of eNOS mRNA in the brain was up-regulated. These results suggest that TFR has protective effects for cerebral injury in rats and mice, which might be associated with its antioxidant properties and ability to regulate the expression of NOS isoforms.

scholarly journals Synergistic Protective Effects of Antioxidant and Nitric Oxide Synthase Inhibitor in Transient Focal Ischemia

1999 ◽  
Vol 19 (2) ◽  
pp. 139-143 ◽  
Author(s):  
Brigitte Spinnewyn ◽  
Sylvie Cornet ◽  
Michel Auguet ◽  
Pierre-Etienne Chabrier
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Infarct Volume ◽  
Ischemia Reperfusion ◽  
Free Radical Scavengers ◽  
Protective Effects ◽  
Nos Inhibitors ◽  
Oxide Synthase

Both nitric oxide synthase (NOS) inhibitors and free radical scavengers have been shown to protect brain tissue in ischemia-reperfusion injury. Nitric oxide and superoxide anion act via distinct mechanisms and react together to form the highly deleterious peroxynitrite. Therefore the authors examined the effects and the interaction between the NOS inhibitor, NG nitro-L-arginine (LNA) and the antioxidant/superoxide scavenger, di-tert-butyl-hydroxybenzoic acid (DtBHB) in the rat submitted to 2 hours of middle cerebral artery occlusion. Posttreatment was initiated 4 hours after the onset of ischemia and infarct volume was measured at 48 hours. The dose-related effect of LNA resulted in a bell-shaped curve: 15, 56, 65, and 33% reduction of total infarct for 0.03, 0.1, 0.3, and 1 mg/kg (intravenously [IV]) respectively and 11% increase in infarct volume for 3 mg/kg (IV). Whereas DtBHB (20 mg/kg; intraperitoneally [IP]) was ineffective, the dose of 60 mg/kg produced 65% protection in infarct volume. The combination of a subthreshold dose of LNA (0.03 mg/kg; IV) and DtBHB (20 mg/kg; IP) resulted in significant reduction (49%) in infarct volume. These results show that LNA and DtBHB act synergistically to provide a consistent neuroprotection against ischemic injury when administered 4 hours after ischemia. This suggests that nitric oxide and free radicals are involved and interact in synergy in ischemia-reperfusion injury.

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